Prospective evaluation of determining the most effective contact for tremor control in patients with deep brain stimulation based on individual tractography (TremTract Study)

脑深部刺激(DBS)是治疗震颤相关疾病的一种公认的治疗方法。最常见的疾病是原发性震颤(ET)和特发性帕金森病(IPS)。对于ET的治疗，DBS导联被植入丘脑腹中核(VIM)，而丘脑下核是IPs的靶点。虽然立体定向DBS手术控制震颤是基于解剖标志，但DBS对震颤的病理生理学理解从靶点特异性效应转向网络特异性效应。关于震颤，有证据表明小脑-丘脑-皮质网络受累。该网络最重要的神经解剖学基础之一是齿状-红-丘脑束(DRTT)。申请人和其他人之前的研究提供的证据表明，DBS可实现的术后震颤控制取决于主动接触DRTT的接近程度。到目前为止，根据目前的临床常规，最有效的接触是由术后麻烦和时间密集(约.3.5小时)临床试验。在临床测试中，每次接触的效果和副作用阈值以0.5 mA为步长确定。拟议研究的目的是前瞻性地评估跨疾病的症状特定震颤网络的假说。这种对病理生理学的理解将转化为临床实践。为了做到这一点，一个高度标准化和自动化的基于成像的管道，基于体素计算刺激扩散和DRTT之间的重叠，将进行前瞻性评估。应用的技术已经在以前的研究中建立，申请者在DBS领域的临床和基于成像的研究方面拥有杰出的专业知识。由于临床测试必须由训练有素的医生进行，因此需要在预期的研究持续时间内为“Wisenschaftliche/r Mitarbeterin/Mitarbeiter”提供资金。在积极评估的情况下，拟议的研究为基于成像的方法确定最有效的震颤控制接触提供了二级证据。在未来，与目前基于临床测试的方法相比，这种方法可以减少患者负担、时间和相关成本。

Deep brain stimulation (DBS) is an established treatment for diseases associated with tremor. The most common diesases are Essential Tremor (ET) and idiopathic Parkinson’s Disease (IPS). For the treatment of ET, DBS leads are implanted in the Nucleus ventralis intermedius oft he thalamus (VIM), whereas the Nucleus subthalamicus is targeted in IPS.While stereotactic DBS surgery for tremor control is based on anatomical landmarks, there is a shift oft the pathophysiological understanding of DBS effects on tremor away from target-point specific effects towards network specific effects. Regarding tremor, there is evidence for the inolvement of cerebello-thalamo-cortical networks. One oft he most important neuroanatomical substrates of this network is the dentato-rubro-thalamic tract (DRTT). Previous studies by the applicant and others provide evidence that the achievable postoperative tremor control by DBS depends on the proximity of the active contact to the DRTT. To date, as per current clinical routine, the most effective contact is postoperatively determined by troublesome and time-intensive (approx. 3.5 hours) clinical testing. During this clinical testing effect and side-effect thresholds are determined in steps of 0.5 mA for each contact.The aim of the proposed study is to evaluate prospectively the hypothesis of a symptom specific tremor network across diseases. This gain of pathophysiological understanding will then be translated to clinical practice. To do so a highly standardized and automatized imaging-based pipeline, based on voxel-based calculation of the overlap between the spread of stimulation and the DRTT, will be prospectively evaluated.The applied techniques were already established during previous studies and the applicant has an outstanding expertise in clinical and imaging-based studies in the field of DBS. As the clinical testing has to be done by a trained physician, funding for a "Ärztliche/r wissenschaftliche/r Mitarbeterin/Mitarbeiter" for the anticipated duration of the study is requested.In case of a positive evaluation, the proposed study provides Class II evidence for an imaging-based approach to determine the most effective contact for tremor control. In the future this approach can lead to a reduction of patient burden, time and related costs in contrast to the current approach based on clinical testing.